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Increased DNA synthesis and immunoglobulin secretion was observed in human peripheral blood lymphocytes (PBL) cultured in vitro with soluble protein A from Staphylococcus aureus (Sp-A). Optimal Ig secretion was obtained in 6 day cultures containing 1 × 106 cells/mI and 10 μg/ml Sp-A. The presence of 5 × 10-5 M 2-mercaptoethanol in the culture medium as well as careful selection of foetal calf serum were needed for optimal results. In response to Sp-A stimulation, the three main classes of immunoglobulins were secreted by PBL. In some individuals, concentration of Sp-A optimal for lgG and IgM secretion inhibited IgA production. Immunoglobulin-con-taming cells were less abundant (0.5-5% of total cells) and smaller in Sp-A than in PWM-stimulated cultures (5-15%). The data suggest that Sp-A and PWM stimulated different subsets of circulating lymphocytes. [ABSTRACT FROM AUTHOR]